This invention relates to a novel monoclonal antibody to human thymidylate synthase and also to a hybridoma capable of producing the same.
Thymidylate synthase (EC2.1.1.45, hereinafter called xe2x80x9cTSxe2x80x9d) is an enzyme that catalyzes a reaction in which thymidylic acid is formed from deoxyuridylic acid, plays a role to supply thymine which is a base specific to DNAs, and is one of principal rate-limiting enzymes for a DNA precursor supply pathway. Accordingly, its activity is known to become higher in thymi or tumor tissues where cell growth is active.
On the other hand, fluoropyrimidine antitumor drugs such as 5-fluorourasil and 5-fluorodeoxyuridine act against TS as a target enzyme, and for example, 5-fluorodeoxyuridine changes into fluorodeoxyuridylic acid in vivo and inhibits TS. In particular, fluoropyrimidine antitumor drugs are known to show high therapeutic effect and significant life prolongation for patients with a low level of TS expression in tumor cells but to exhibit low therapeutic effect for patients with TS in a high level [xe2x80x9cGan to Kagaku Ryoho (Cancers and Chemotherapy)xe2x80x9d, 24(6), 705-721 (1997)]. The measurement of TS is therefore important, for example, an advance measurement of the expression of TS in an excised tumor upon treatment for a cancer patient gives indications for the determination of a treatment method and for the selection of an antitumor drug.
An object of the present invention is therefore to provide an anti-human TS monoclonal antibody useful for the immunological measurement of human TS and also a hybridoma capable of producing the same.
With the foregoing circumstances in view, the present inventors have proceeded with various investigations. As a result, novel anti-human TS monoclonal antibodies have been obtained and moreover, these monoclonal antibodies have been confirmed to be useful for the immunological measurement of human TS, leading to the completion of the present invention.
The present invention therefore provides an anti-human TS monoclonal antibody capable of recognizing an epitope which exists in a region of 187th to 313th amino acids from an N-terminus in human TS, an anti-human TS monoclonal antibody capable of recognizing an epitope which exists in a region of from an N-terminus to a 61st amino acid in human TS, and also hybridomas capable of producing these monoclonal antibodies.
Incidentally, the recognition regions by the human TS monoclonal antibodies according to the present invention have been determined in accordance with the amino acid sequence of human TS described, for example, in Nucleic Acids Research, 13(6), 2035-2043 (1985) or the like.